Estrogens are essential regulators of fertility and bind to estrogen receptors (ERs) ERalpha and ERbeta. The extent to which signalling through ERbeta modulates human fertility is still unclear. Immunohistochemistry revealed that many cells within male and female reproductive systems synthesize ERbeta. Studies using mice lacking functional ERbeta demonstrated disturbed ovarian but intact testicular, function. Differences in reproductive physiology and in ESR expression patterns in rodents and humans mean that we need more data from studies using human cells and/or primate models before we can unravel the contribution made by ERbeta, or its variant isoforms, to reproductive function in humans. Available evidence suggests that direct targeting of ERbeta with selective agonists and antagonists might provide a novel therapeutic target in fertility and/or infertility management.